"If PFS difference between the cohorts falls short of significantly it does not mean that the study is destined to fail, and that the vaccine is nothing but a placebo." RK
RK, I respect your viewpoints a lot. With that said, I will try to make my point a little clearer. If the PFS difference in the ITT population falls short of significance, it means the p3 study has FAILED. It does NOT mean that the vaccine is nothing but a placebo BUT this trial is NOT designed properly to answer the OS question adequately. The enhancements made the last time was far from sufficient to answer that OS question because it still was not powered sufficiently and no one knows whether there was any alpha assigned to that end point in the first place. So I won't go that far and call this vaccine nothing more than placebo, but at the same time I will make the stance that its effectiveness is minimal for most GBM patients except for some sub-grps. Again, unfortunately, when I found out that this p3 trial design deviated from their earlier pI trials, then even my hope for sub-grp positive data got diminished. (Though from a skeptics point of view, even the very promising results from their pI trials could be explained by unintentional cherry picked patients- basically a false positive).
Again, I don't blame the company for the initial trial design for this p3 since they inherited it from UCLA, but all the post decisions to enhance it and change it to a p3 trial was IMO a great waste of time and resources. I do blame the company for its lack of transparency and lack of proper disclosure of material information as well as their unethical related party transactions.
So, RK you decided to jump in again cautiously into NWBO. What positive are you anticipating near term to support that decision? That the hold will be lifted soon? (The company gave a new warning in their 10K that it may never be lifted.) The investigation will be completed soon? (I'm not expecting much from an investigative team picked by LP.) TA showing a strong upward trend? (It failed at the 2.39 mark and has been in a steady downtrend and this current turn may be a false one.) Direct to save the day? (Why the delay in starting the p2 portion. Company had indicated that the way the pI/II Direct trial was designed allowed a seamless transition to the enlarged p2 portion. All we got was delay. IMO as you already know, Direct was a failure to show any ORR and therefore again IMO it will be a waste to explore it seeking OS/PFS as its endpoints. Again, all this talk about trying to change this current p3 trial like the last time will IMO be pointless since I strongly believe an IA was done last summer in July. I cannot fathom the FDA allowing changes to this trial AFTER a IA efficacy determination was made (my assumption of course) even if the OS showed that "everyone is living longer". Another p3 trial that is better designed would solve that problem easily. What, it's not a new concept to run several p3 trials before approval. Even the company warned about that possibility in their 10K.
"Let's say that an IA was done in August, as you suggest it was, if the study proved completely futile then the decision to end it would be easy one. However we sit at a "no decision had been made" point in time. The only thing we know is that there is a risk that regulators may not lift the screening halt. If AVII is correct and the independent radiologist review are determining PFS events, and those turn out not to be "true" PFS events (due to immunotherapy inducing psPD condition) then those patients will crossover and in theory go on to live a long time. That early PFS event would have a negative affect on the TX arm's ability to show a time to progression difference if it occurs often enough in the TX cohort. But on the flip side, overall survival would be extended for those early event patients, hopefully you see that. " RK
A DMC decision IMO most likely was made. Non-disclosure of that does not mean that a no decision had been made. It may only mean that the company decided that they can choose what and when to PR material information. I strongly believe that AVII is correct which also supports those who believe that PFS does not correlate to OS so that the primary endpoint for GBM studies have to be OS. Also, all claims by Dr. Liau that all patients are living longer does NOT mean that the vaccine is the reason for those patients living longer. If there is no difference due to cross-over, the efficacy question remains unanswered. IMO cross-over is not the problem, it is the efficacy of the vaccine that is the problem. Any extended OS is most likely due to what you observed- a better SOC.
JMHO because this company is so non-transparent- which is a bad thing for investors.
